Basal-like breast tumors are aggressive cancers associated with high proliferation and metastasis. Basal-like breast cancers lack expression of estrogen receptor (ER), progesterone receptor (PR), and epidermal growth factor receptor-2 (HER2). Some extremely aggressive basal-like breast cancers are also associated with hypoxia, inflammation and high leukocyte infiltration. The presence of stem-cell-like signatures is a hallmark of these tumors. The response of these cancer types to first-line chemotherapy is often hindered by developed resistance to treatment, recurrence, and metastatic disease. High expression of inflammation and angiogenesis-related metagenes are associated with poor prognosis. Importantly, there is a lack of selective therapeutic agents to target these tumors and patients are left only with chemotherapy options.
Recent large-scale studies of breast carcinomas have elucidated the fundamental role of Transcription Factors (TFs) as driving forces of oncogenesis in basal-like cancers. Notably, many developmental Homeodomain (HD) containing TFs (TFHDs) are aberrantly expressed in cancer and are drivers of cancer initiation, disease recurrence, and resistance to treatment. However, despite their critical role in cancer, TFs have not been successfully targeted with conventional small molecules and have been considered “undruggable”.
The preceding discussions of the background art is intended to facilitate an understanding of the present invention only. The discussion is not an acknowledgement or admission that any of the material referred to is or was part of the common general knowledge as at the priority date of the application.